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Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

This study has been completed.
Sponsor:
Information provided by:
Action Pharma A/S
ClinicalTrials.gov Identifier:
NCT00903604
First received: May 15, 2009
Last updated: May 16, 2011
Last verified: May 2011
  Purpose

The purpose of the present research study is to investigate the pharmacokinetics, as well as safety, tolerability and pharmacodynamics of different ascending dosing regimens of AP214 in patients undergoing cardiac surgery. AP214, the investigational drug, is being developed to potentially prevent post-surgical kidney injury after thoracic aortic aneurysm repair.


Condition Intervention Phase
Cardiac Surgery
Coronary Artery Bypass Grafting
Valve Surgery
Aortic Root or Ascending Aortic Aneurysm Repair Surgery
Drug: AP214
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by Action Pharma A/S:

Primary Outcome Measures:
  • To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery. [ Time Frame: Day 0 to Day 1 ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of AP214, defined as a descriptive analysis of AEs and SAEs (including analysis of severity and relationship to trial drug) [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess effect of AP214 on cardiac surgery induced systemic inflammation o determined by the post-operative peak plasma concentrations of TNF-α, IL-6, IL-8, and IL-10, and area under the curve (AUC) for TNF-α, IL-6, IL-8, and IL-10 [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
  • To assess effect of AP214 on development of post-surgical acute kidney injury (AKI), where AKI is evaluated by evaluation of serum creatinine values, urine output and renal replacement therapy free days. [ Time Frame: Day 0 - Day 30 ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of AP214 on standard safety laboratory data [ Time Frame: Day 0-14 ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of AP214 on vital signs [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]
  • To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]
  • To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically. [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: May 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AP214
Infusions of sequential ascending dosages of AP214
Drug: AP214
Three 10-minutes infusions of sequential ascending dosages of AP214
Placebo Comparator: Placebo
Infusions of saline solution
Drug: Placebo
Three 10-minutes infusions of isotonic saline solution

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has signed the trial-specific informed consent form.
  2. Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized, e.g. tubal ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
  3. Patients undergoing CABG, valve(s), CABG/valve(s) and/or aortic root or ascending aortic aneurysm repair surgery.
  4. Cleveland Clinic Renal Score ≥ 2 (higher than average risk for AKI).
  5. EF ≥ 30%, evaluated within 2 months prior to screening visit.

Exclusion Criteria:

  1. Cardiac surgery to be performed "off pump" without cardiopulmonary bypass.
  2. Circulatory arrest in connection with aortic root or ascending aortic aneurysm repair surgery.
  3. Confirmed or suspected endocarditis.
  4. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
  5. Receiving Aprotinin during the trial, from Screening to Day 90.
  6. Having undergone cardiovascular catheterization ≤ 48 hours prior to scheduled surgery.
  7. Active peptic ulcer disease and gastritis.
  8. Hemoccult positive stools, hematological, bleeding, and coagulation disorders.
  9. Receiving dopamine at renal doses (2-4 mcg/kg/min), from Screening to Day of surgery.
  10. S-Creatinine greater than 2.1 mg/dl.
  11. Known or suspected hypersensitivity to the investigational medicinal product.
  12. Known or suspected hypersensitivity to Ondansetron or other selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
  13. Current participation in any other interventional clinical trial.
  14. Previously dosed with AP214.
  15. Use of investigational medicinal products within the previous 6 months.
  16. Body weight above 140 kg.
  17. History of any organ transplant.
  18. Women who are of childbearing potential, pregnant, or breast-feeding.
  19. Current abuse of alcohol or substance, according to the investigator's medical judgment.
  20. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures.
  21. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903604

Locations
Denmark
Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark, 2100
Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery
Odense, Denmark, 5000
Sponsors and Collaborators
Action Pharma A/S
Investigators
Principal Investigator: Daniel Steinbrüchel, Professor Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet
  More Information

No publications provided

Responsible Party: Action Pharma A/S
ClinicalTrials.gov Identifier: NCT00903604     History of Changes
Other Study ID Numbers: AP214-CS005
Study First Received: May 15, 2009
Last Updated: May 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Action Pharma A/S:
Cardiac surgery
coronary artery bypass grafting
valve surgery
aortic root or ascending aortic aneurysm repair surgery
Acute kidney injury

Additional relevant MeSH terms:
Aneurysm
Aortic Aneurysm
Aortic Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 23, 2014